Interleukin-7-dependent nonclassical monocytes and CD40 expression are affected in children with type 1 diabetes

Eur J Immunol. 2021 Dec;51(12):3214-3227. doi: 10.1002/eji.202149229. Epub 2021 Nov 1.


The important role of IL-7 in the generation of self-reactive T-cells in autoimmune diseases is well established. Recent studies on autoimmunity-associated genetic polymorphisms indicated that differential IL-7 receptor (IL-7R) expression of monocytes may play a role in the underlying pathogenesis. The relevance of IL-7-mediated monocyte functions in type 1 diabetes remains elusive. In the present study, we characterized monocyte phenotype and IL-7-mediated effects in children with type 1 diabetes and healthy controls with multicolor flow cytometry and t-distributed Stochastic Neighbor-Embedded (t-SNE)-analyses. IL-7R expression of monocytes rapidly increased in vitro and was boosted through LPS. In the presence of IL-7, we detected lower monocyte IL-7R expression in type 1 diabetes patients as compared to healthy controls. This difference was most evident for the subset of nonclassical monocytes, which increased after IL-7 stimulation. t-SNE analyses revealed IL-7-dependent differences in monocyte subset distribution and expression of activation and maturation markers (i.e., HLA-DR, CD80, CD86, CD40). Notably, monocyte CD40 expression increased considerably by IL-7 and CD40/IL-7R co-expression differed between patients and controls. This study shows the unique effects of IL-7 on monocyte phenotype and functions. Lower IL-7R expression on IL-7-induced CD40high monocytes and impaired IL-7 response characterize monocytes from patients with type 1 diabetes.

Keywords: CD40 antigens; autoimmunity; interleukin-7; monocytes; type 1 diabetes.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • CD40 Antigens / immunology*
  • Child
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Gene Expression Regulation / immunology*
  • Humans
  • Interleukin-7 / immunology*
  • Interleukin-7 Receptor alpha Subunit / immunology
  • Male
  • Monocytes / immunology*


  • CD40 Antigens
  • IL7 protein, human
  • IL7R protein, human
  • Interleukin-7
  • Interleukin-7 Receptor alpha Subunit